Abstract 1403: Comprehensive characterization of 1038 Chinese non-small cell lung cancer patients of different PD-L1 expression levels
Authors: Weiqiang Yin, Jinghao Liang, Zhihua Guo, Zixian Xie, Haonan Zhao, Fayuan Wu
Journal: Cancer Research (2023)

Abstract Background: Programmed death ligand 1 (PD-L1) is currently one of the most well-characterized markers for predicting response to immunotherapy in non-small cell lung cancer (NSCLC). Multiple clinicohistologic and genetic characteristics have been proposed as correlates of PD-L1 expression. However, few studies have examined the associations between PD-L1 expression and immune infiltration or chromosomal arm-level alterations. In this comprehensive characterization, we identified clinical features, oncogenic drivers and other genomic abnormalities, impaired biological pathways, arm-level amplifications and losses, and infiltration of immune cell populations that were associated with PD-L1 expression. Methods: We retrospectively included 1038 NSCLC patients who had both PD-L1 Tumor Proportion Score (TPS) by the 22C3 assay and genomic profiles acquired with targeted sequencing using 8-, 168-, and 520-gene panels (Burning Rock Biotech, Guangzhou, China). Multiplex immunohistochemistry (mIHC) was used to analyze immune infiltration. Association analysis was performed to identify patient characteristics associated with PD-L1 expression. Results: The negative (TPS &amp;lt;1%), low (1-49%), and high (≥50%) PD-L1 expression classes accounted for 25.2% (n = 262), 43.2% (n = 449), and 31.5% (n = 327) patients, respectively. PD-L1 expression was positively associated with advanced tumor stage, the male sex, squamous carcinoma, ALK fusions, KRAS G12/13X mutations, BRAF V600E, ROS1 fusion, MET exon 14 skipping, altered TP53, LPR1B, FAT1, PTPRD, KDR, and CD274, and altered pathways such as MAPK, RAS, DNA damage response, p53 signaling, and checkpoint factors. The negative correlates included driver-positive status, EGFR L858R, EGFR exon 19 deletions, ERBB2 exon 20 insertions, altered RMB10, STK11, RICTOR, GNAS, and PIK3C2G, and aberrant receptor tyrosine kinase, ERBB2 signaling, and non-homologous end joining. In terms of arm-level aberrations, PD-L1 positivity was associated with 3p, 3q, 7p or 7q amplification and 18p, 20p, or 20q deletion. We also found that 9p, 9q, 10p, 12p, 12q, and 19p amplifications were most frequent in high PD-L1-high patients, who were also more likely to harbor 18p, 29p, or 20q deletion when compared with compared with PD-L1-negative patients. mIHC analysis revealed that PD-L1 expression was associated with proportions of CD3+, CD3+CD8+, CD3+PD-1+, CD8+PD-1+, and PD-1+ cells in the tumor and CD3+PD-1+, CD8+PD-1+, and PD-1+ cells in the stroma, suggesting increased tumor infiltration of cytotoxic T cells associated with PD-L1 expression. Conclusions: This study provides a comprehensive analysis of the associations between PD-L1 expression and a multitude of histopathologic, genomic, and immunologic features. Further research is warranted for validation and association of these factors with clinical outcomes. Citation Format: Weiqiang Yin, Jinghao Liang, Zhihua Guo, Zixian Xie, Haonan Zhao, Fayuan Wu. Comprehensive characterization of 1038 Chinese non-small cell lung cancer patients of different PD-L1 expression levels [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1403.